**7. Prevention of further spread of AMR**

The extent to which AMR has spread is due to the selective pressure provided by extensive antibiotic consumption and usage. Strategies to curtail the human use of antibiotic include antibiotic stewardship, public awareness to avoid self-medication, use of antibiotics in therapeutic doses and for appropriate length of time and education and counselling to patients not to pressurise the clinician into prescribing antibiotics for trivial illnesses. Development of new rapid diagnostic point of care tests will inform the clinician not to use antibiotics in the viral infections.

human health problem but is an ecological challenge as well. It is up to the human race to take

[1] Nelson ML, Dinardo A, Hochberg J, Armelagos GJ. Brief communication: Mass spectroscopic characterization of tetracycline in the skeletal remains of an ancient population from Sudanese Nubia 350-550 CE.American Journal of Physical Anthropology. 2010;**143**:151-154

[2] Sobell HM. Actinomycin and DNA transcription. Proceedings of the National Academy

[3] Garau G, Di Guilmi AM, Hall BG. Structure-based phylogeny of the metallo-beta-lacta-

[4] Ehrlich P, Hata S. Die Experimentelle Chemotherapie der Spirilosen. Berlin: Julius

[5] Fleming A. On antibacterial action of culture of Penicillium, with special reference to their use in isolation of *B. influenzae*. British Journal of Experimental Pathology. 1929;**10**:226-236

[6] Chain E, Florey HW, Gardner AD, Heatley NG, Jennings MA, Orr-Ewing J, et al. The classic: Penicillin as a chemotherapeutic agent. Clinical Orthopaedics and Related Research.

[7] Ventola CL.The antibiotic resistance crisis part 1: Causes and threats. P&T. 2015;**40**:277-283 [8] Fasugba O, Gardner A, Mitchell BG, Mnatzaganian G. Ciprofloxacin resistance in community- and hospital-acquired *Escherichia coli* urinary tract infections: A systematic review and meta-analysis of observational studies. BMC Infectious Diseases. 2015;**15**:1-16

[9] Sengupta S, Chattopadhyay MK, Grossart HP. The multifaceted roles of antibiotics and

[10] Center for Disease Control and Prevention. Office of Infectious Disease. Antibiotic resistance threats in the United States. 2013. Available from: http://www.cdc.gov/drugresistance/

antibiotic resistance in nature. Frontiers in Microbiology. 2013;**4**:47

and Yashwant Kumar<sup>2</sup>

Introductory Chapter: Stepping into the Post-Antibiotic Era—Challenges and Solutions

http://dx.doi.org/10.5772/intechopen.84486

9

, Ajay Kumar Tahlan<sup>2</sup>

1 Postgraduate Institute of Medical Education and Research, Chandigarh, India

of Sciences of the United States of America. 1985;**82**:5328-5331

mases. Antimicrobial Agents and Chemotherapy. 2005;**49**:2778-2784

up this challenge and save the world from this menace.

, Shveta Sethi1

\*Address all correspondence to: yasht26@yahoo.co.in

2 Central Research Institute, Kasauli, Himachal Pradesh, India

**Author details**

Neelam Taneja1

**References**

Springer; 1910

2005;**439**:23-26

threat-report-2013

#### **7.1. Regulation in human as well livestock sector**

Though a sticky and complex issue, regulation of unprescribed antibiotics is essential especially in developing countries. There should be the rule of "prescription-only medicines" similar to various international guidelines [42]. In the veterinary and agriculture set-up, antibiotic usage is linked to economic gains. Scandinavian countries set up a good example to follow by not using antibiotics as growth promoters, and they do have the least AMR issues [43].

#### **7.2. Antibiotic stewardship**

Antimicrobial stewardship refers to "The optimal selection, dosage, and duration of antimicrobial treatment that results in the best clinical outcome for the treatment or prevention of infection, with minimal toxicity to the patient and minimal impact on subsequent resistance" [44]. Hence, antimicrobial stewardship basically aims at helping each patient receive the appropriate treatment without adverse effects of antibiotic use. These programmes are beneficial in reducing treatment failures, decreasing health-care associated infections and also reducing antibiotic resistance while proving economically beneficial to the hospital.

#### **7.3. Connecting human, animal and environmental health: One Health Approach**

In 2003, in an interview, a journalist used the word "One Health" by saying that "Human or livestock or wildlife health can't be discussed in isolation anymore-there is just one health" [45]. Since then "One Health" concept has gained more recognition in the public health and animal health communities. "One Health" is a collaborative approach among various sectors and disciplines to achieve optimal health outcomes emphasising the relation between humans, animals, plants and environment shared by them [46]. This is the need of the hour because many diseases are zoonotic in nature, and microbes harbouring drug-resistant genes have no barriers. Now the WHO and CDC have also adopted this approach.

## **8. Conclusions**

The AMR is marching globally and threatens to undo the extraordinary advancements achieved in human medicine. Coordinated efforts are required across the globe to manage this great crisis. It is time we learn from our mistakes and gather our act together to outsmart the bacteria. All said and done, microbes do have an evolutionary advantage of nearly 4 billion years and have learnt to survive the onslaught of antibiotics. We can learn from them by using the sophisticated molecular approaches we have. Antimicrobial resistance is not only a human health problem but is an ecological challenge as well. It is up to the human race to take up this challenge and save the world from this menace.

## **Author details**

stewardship, public awareness to avoid self-medication, use of antibiotics in therapeutic doses and for appropriate length of time and education and counselling to patients not to pressurise the clinician into prescribing antibiotics for trivial illnesses. Development of new rapid diagnostic point of care tests will inform the clinician not to use antibiotics in the viral infections.

Though a sticky and complex issue, regulation of unprescribed antibiotics is essential especially in developing countries. There should be the rule of "prescription-only medicines" similar to various international guidelines [42]. In the veterinary and agriculture set-up, antibiotic usage is linked to economic gains. Scandinavian countries set up a good example to follow by not using antibiotics as growth promoters, and they do have the least AMR issues [43].

Antimicrobial stewardship refers to "The optimal selection, dosage, and duration of antimicrobial treatment that results in the best clinical outcome for the treatment or prevention of infection, with minimal toxicity to the patient and minimal impact on subsequent resistance" [44]. Hence, antimicrobial stewardship basically aims at helping each patient receive the appropriate treatment without adverse effects of antibiotic use. These programmes are beneficial in reducing treatment failures, decreasing health-care associated infections and also reducing antibiotic resistance while proving economically beneficial

**7.3. Connecting human, animal and environmental health: One Health Approach**

have no barriers. Now the WHO and CDC have also adopted this approach.

In 2003, in an interview, a journalist used the word "One Health" by saying that "Human or livestock or wildlife health can't be discussed in isolation anymore-there is just one health" [45]. Since then "One Health" concept has gained more recognition in the public health and animal health communities. "One Health" is a collaborative approach among various sectors and disciplines to achieve optimal health outcomes emphasising the relation between humans, animals, plants and environment shared by them [46]. This is the need of the hour because many diseases are zoonotic in nature, and microbes harbouring drug-resistant genes

The AMR is marching globally and threatens to undo the extraordinary advancements achieved in human medicine. Coordinated efforts are required across the globe to manage this great crisis. It is time we learn from our mistakes and gather our act together to outsmart the bacteria. All said and done, microbes do have an evolutionary advantage of nearly 4 billion years and have learnt to survive the onslaught of antibiotics. We can learn from them by using the sophisticated molecular approaches we have. Antimicrobial resistance is not only a

**7.1. Regulation in human as well livestock sector**

**7.2. Antibiotic stewardship**

8 Antimicrobial Resistance - A Global Threat

to the hospital.

**8. Conclusions**

Neelam Taneja1 , Shveta Sethi1 , Ajay Kumar Tahlan<sup>2</sup> and Yashwant Kumar<sup>2</sup>


## **References**


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**Chapter 2**

**Provisional chapter**

**Antimicrobial Resistance of Common Zoonotic Bacteria**

**Antimicrobial Resistance of Common Zoonotic Bacteria** 

Antimicrobial resistance in the food chain is currently a subject of a major interest. The excessive use or rather misuse of antimicrobials coupled with a poor hygiene in the food production chain has led to a rise of resistant zoonotic bacteria, commonly transmitted by food. They pose a serious threat to human health. Campylobacteriosis is the leading bacterial food-borne illness and most commonly reported zoonosis in humans in the European Union for more than a decade. Salmonellosis is most frequently diagnosed in food-borne outbreaks. Fluoroquinolones are considered as critically important for treatment of severe cases of both zoonoses in humans. Due to an extremely prevalent resistant isolates, especially from broilers and meat, also the treatment of human *Campylobacter* infections with fluoroquinolones has become compromised. *Salmonella* isolates from poultry and poultry meat tend to be highly resistant to fluoroquinolones as well. Beside the resistance to this group of antibiotics, the threat of multiple drug resistant (MDR) *Campylobacter* and *Salmonella* strains is discussed in the light of most recent reports of

**Keywords:** *Campylobacter*, *Salmonella*, antimicrobial resistance, food safety, food

Antimicrobials are indispensable in human medicine for treating and preventing infectious diseases. In addition, the same classes of antimicrobials are extensively used in livestock not only for the treatment and prevention of infections but also for the growth promotion [1]. The

latter has, however, been banned in the European Union (EU) since 2006 [2].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

© 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

distribution, and reproduction in any medium, provided the original work is properly cited.

DOI: 10.5772/intechopen.80782

**in the Food Chain: An Emerging Threat**

**in the Food Chain: An Emerging Threat**

Vita Rozman, Bojana Bogovič Matijašić and

Vita Rozman, Bojana Bogovič Matijašić

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

animal, food and human clinical surveillance systems.

production chain, multiple drug resistance

http://dx.doi.org/10.5772/intechopen.80782

Sonja Smole Možina

**Abstract**

**1. Introduction**

and Sonja Smole Možina


#### **Antimicrobial Resistance of Common Zoonotic Bacteria in the Food Chain: An Emerging Threat Antimicrobial Resistance of Common Zoonotic Bacteria in the Food Chain: An Emerging Threat**

DOI: 10.5772/intechopen.80782

Vita Rozman, Bojana Bogovič Matijašić and Sonja Smole Možina Vita Rozman, Bojana Bogovič Matijašić and Sonja Smole Možina

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/intechopen.80782

#### **Abstract**

[39] Rossolini GM, Arena F, Pecile P, Pollini S. Update on the antibiotic resistance crisis.

[40] Poudyal A, Yu HH, Matthaiou DK. Colistin and doripenem combinations demonstrate synergy and suppression of resistance against *Acinetobacter baumannii* at multiple inocula in an in vitro PK/PD Model. In: 21st European Congress of Clinical Microbiology

[41] Viertel TM, Ritter K, Horz HP. Viruses versus bacteria-novel approaches to phage therapy as a tool against multidrug-resistant pathogens. Journal of Antimicrobial

[42] Davies SC. Reducing inappropriate prescribing of antibiotics in English primary care: Evidence and outlook. Journal of Antimicrobial Chemotherapy. 2018;**73**:833-834

[43] Bengtsson B, Wierup M. Antimicrobial resistance in Scandinavia after ban of antimicro-

[44] Gerding DN. The search for good antimicrobial stewardship. Joint Commission Journal

[45] Weiss R. Africa's Apes Are Imperiled, Researchers Warn. The Washington Post. Apr. 7,

bial growth promoters. Animal Biotechnology. 2006;**17**:147-156

[46] Available from: https://www.cdc.gov/onehealth/index.html

Current Opinion in Pharmacology. 2014;**18**:56-60

And Infectious Diseases (ECCMID); Milan. 2011

Chemotherapy. 2014;**69**:2326-2336

12 Antimicrobial Resistance - A Global Threat

on Quality Improvement. 2001;**27**:403-404

2003

Antimicrobial resistance in the food chain is currently a subject of a major interest. The excessive use or rather misuse of antimicrobials coupled with a poor hygiene in the food production chain has led to a rise of resistant zoonotic bacteria, commonly transmitted by food. They pose a serious threat to human health. Campylobacteriosis is the leading bacterial food-borne illness and most commonly reported zoonosis in humans in the European Union for more than a decade. Salmonellosis is most frequently diagnosed in food-borne outbreaks. Fluoroquinolones are considered as critically important for treatment of severe cases of both zoonoses in humans. Due to an extremely prevalent resistant isolates, especially from broilers and meat, also the treatment of human *Campylobacter* infections with fluoroquinolones has become compromised. *Salmonella* isolates from poultry and poultry meat tend to be highly resistant to fluoroquinolones as well. Beside the resistance to this group of antibiotics, the threat of multiple drug resistant (MDR) *Campylobacter* and *Salmonella* strains is discussed in the light of most recent reports of animal, food and human clinical surveillance systems.

**Keywords:** *Campylobacter*, *Salmonella*, antimicrobial resistance, food safety, food production chain, multiple drug resistance

#### **1. Introduction**

Antimicrobials are indispensable in human medicine for treating and preventing infectious diseases. In addition, the same classes of antimicrobials are extensively used in livestock not only for the treatment and prevention of infections but also for the growth promotion [1]. The latter has, however, been banned in the European Union (EU) since 2006 [2].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2018 The Author(s). Licensee IntechOpen. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The amounts of antimicrobials utilised in livestock are vast and often exceed those in humans. Data suggest that in the EU approximately 70% of antimicrobials were sold for use in livestock in 2014 [3]. The consumption of antimicrobials in humans and animals has indeed been associated with the occurrence of antimicrobial resistance (AMR) in zoonotic bacteria [3], which are the causative agents of zoonoses and can be transmitted directly between animals and humans or *via* the food chain. AMR in zoonotic bacteria is a subject of major concern.

Even though AMR is an ancient and naturally occurring phenomenon in some bacteria [4], the excessive use of antimicrobials in humans and livestock, as well as poor hygiene conditions and practices in the food production chain, accelerates the emergence of resistance in zoonotic bacteria [5]. The alarming consequence of AMR coupled with the paucity of novel antimicrobials is the rise in the frequency of multidrug resistant (MDR) zoonotic bacteria that may lead to an impaired response to antimicrobial therapy or ultimately even treatment failure [6].

The most current data regarding AMR in zoonotic bacteria are published annually by European Food Safety Authority (EFSA) and European Centre for Disease Control and Prevention (ECDC), but usually with a two-year delay in publishing. According to the recent report on AMR in zoonotic bacteria in 2016 [5], resistance in *Salmonella* and *Campylobacter* is considered of the highest concern. The scope of this review is, therefore, to discuss and emphasise the current trends of AMR in *Salmonella* and *Campylobacter* in the light of the recent EFSA/ECDC report, and the role of whole genome sequencing (WGS) in the surveillance of AMR in *Salmonella* and *Campylobacter* along the food production chain.

In the Member States (MS) of the EU monitoring and reporting data on zoonoses and AMR for *Salmonella* and *Campylobacter* from animals, food, feed and humans are mandatory [10]. Comparing AMR data from different countries and assessing trends has long been challenging due to inadequate harmonisation of the methodology and reporting among the MS [11]. Recently, great progress has been made in terms of harmonisation of AMR surveillance programs, especially for food animals and foods with the new legislation [12]. In addition, a protocol for harmonised monitoring of AMR in humans has been developed [13], but it is not

Antimicrobial Resistance of Common Zoonotic Bacteria in the Food Chain: An Emerging Threat

http://dx.doi.org/10.5772/intechopen.80782

15

According to the recent report on trends and sources of zoonoses, zoonotic agents and foodborne outbreaks in 2016 published by EFSA/ECDC [7], the declining trend of salmonellosis in Europe has ended. In 2016, there were 94,530 confirmed cases of salmonellosis with the highest notification rate per 100,000 population in Eastern Europe (in average 46.9 per 100,000), mostly on the account of Czech Republic (110) and Slovakia (97.7), followed by Northern (20.6), Western (18.8) and Southern Europe (13.0). Additionally, *Salmonella* was most regularly detected in food-borne outbreaks (22.3%), which have resulted in the highest burden of hospitalisations (45.6% of the total number of hospitalised cases) and deaths (50% of the total number of deaths among outbreak cases) [7]. Outbreaks were linked to several sources, e.g.,

*Salmonella* was the most prevalent in meat from turkeys (7.74% of the samples tested positive) and from broilers (6.39%), as well as dried seeds (8.0%) [7], which are an important source of infections, especially due to a long shelf life and low moisture [17]. Chicken, turkey and other avian species are commonly inhabited with *Salmonella* without noticeable symptoms [18], which is in addition to the practices in the food production chain [19], considered the highest risk for contamination of meat products. Even though *Salmonella* was significantly less frequently detected in eggs and their products, they remain the most important source

a legal document that would obligate the MS to its implementation.

**Figure 1.** Common zoonoses in Europe in 2016. STEC: Shiga toxin-producing *Escherichia coli* [7].

**3.1. Prevalence of nontyphoidal** *Salmonella* **in the food chain**

Polish eggs [14], infant formula [15] and sesame seeds [16].

**3.** *Salmonella*

## **2. Common zoonoses in Europe**

For more than a decade, campylobacteriosis has been the most common zoonosis in Europe. Salmonellosis is the second most commonly reported enteric infection, and the leading cause of food-borne outbreaks. *Campylobacter* and *Salmonella* combined accounted for almost 95% of the reported and confirmed zoonoses cases in 2016 (**Figure 1**).

Salmonellosis is a food-borne gastrointestinal infection caused by zoonotic bacteria *Salmonella* spp. Several thousand serovars of *Salmonella* spp. *enterica* exist, yet only some are causing disease symptoms. Nontyphoidal serovars are transmitted *via* the food chain, whereas typhoidal serovars, the causative agents of typhoid fever, are restricted to humans [8]. Whilst the majority of nontyphoidal *Salmonella* infections are self-limiting and do not require any antibiotic treatment, some cases result in life-threatening systemic infections that must be treated with antimicrobials, primarily fluoroquinolones (FQ) or third-generation cephalosporins [5]. Resistance to these drugs may jeopardise the efficiency of the antimicrobial therapy.

*Campylobacter* spp. are common gut commensals of several animal species, especially birds [9], and the leading cause of gastroenteritis in humans, yet the infections often go unreported. The majority of campylobacterioses are caused by two species, namely *Campylobacter jejuni* and *Campylobacter coli*. Symptoms of campylobacteriosis are also usually mild and self-limiting, although some patients with acute infections that can trigger autoimmune inflammatory conditions need to be treated with antimicrobials, primarily macrolides and FQ [5]. Emergence of resistance in *Campylobacter* is common and thus of concern.

Antimicrobial Resistance of Common Zoonotic Bacteria in the Food Chain: An Emerging Threat http://dx.doi.org/10.5772/intechopen.80782 15

**Figure 1.** Common zoonoses in Europe in 2016. STEC: Shiga toxin-producing *Escherichia coli* [7].

In the Member States (MS) of the EU monitoring and reporting data on zoonoses and AMR for *Salmonella* and *Campylobacter* from animals, food, feed and humans are mandatory [10]. Comparing AMR data from different countries and assessing trends has long been challenging due to inadequate harmonisation of the methodology and reporting among the MS [11]. Recently, great progress has been made in terms of harmonisation of AMR surveillance programs, especially for food animals and foods with the new legislation [12]. In addition, a protocol for harmonised monitoring of AMR in humans has been developed [13], but it is not a legal document that would obligate the MS to its implementation.
